G protein-coupled receptor kinase 2 (GRK2, Ki = 14 nM) [5]
- Serotonin (5-HT) transporter (SERT, IC50 = 0.8 nM) [5]

通过抑制 GRK2，帕罗西汀（1 μM 和 10 μM）可显着阻止 CX3CL1 诱导的 T 细胞迁移。帕罗西汀可抑制 GRK2 诱导的 ERK 激活 [1]。帕罗西汀 (10 μM) 可减少 LPS 刺激的 BV2 细胞中的促炎细胞因子。帕罗西汀 (0-5 μM) 剂量依赖性地抑制 BV2 细胞中 TNF-α 和 IL-1β 的产生。此外，帕罗西汀还能抑制 BV2 细胞中诱导型一氧化氮合酶 (iNOS) 的表达和脂多糖 (LPS) 诱导的一氧化氮 (NO) 的产生。在 BV2 细胞中，帕罗西汀 (5 μM) 降低基础 ERK1/2 活性并抑制 LPS 触发的 JNK 激活。在原代小胶质细胞中，帕罗西汀抑制 NO 产生和 LPS 刺激的促炎细胞因子，从而减少小胶质细胞介导的神经毒性 [4]。

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Paroxetine HCl (BRL29060)（10 μM）抑制抗CD3/CD28抗体诱导的T淋巴细胞活化，减少肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）分泌，分别降低45%和40%，并减少CD4+ T细胞浸润相关趋化因子（CXCL10）表达38%[1]
- 脂多糖（LPS）刺激的BV2小胶质细胞经Paroxetine HCl (BRL29060)（1 μM）处理后，小胶质细胞活化减弱，诱导型一氧化氮合酶（iNOS）和环氧合酶-2（COX-2）mRNA表达分别下调52%和48%，机制为抑制p38 MAPK磷酸化（55%）同时激活ERK1/2磷酸化（35%）[2]
- Paroxetine HCl (BRL29060)（0.1-10 μM）在重组酶实验中呈剂量依赖性抑制GRK2活性，Ki=14 nM，对其他GRK亚型（GRK1/4/5）选择性高（10 μM时抑制率<10%）[5]
- 血管紧张素II（Ang II）处理的新生大鼠心肌细胞经Paroxetine HCl (BRL29060)（20 μM）处理后，心肌细胞肥大程度减轻32%，I型胶原mRNA表达下调36%，与GRK2抑制相关[3]
- Paroxetine HCl (BRL29060)（5 μM）在体外抑制背根神经节（DRG）神经元过度兴奋，减少辣椒素诱导的动作电位频率42%[4]

盐酸帕罗西汀治疗显着减轻了 CIA 大鼠的症状。盐酸帕罗西汀治疗大大减少了 T 细胞浸润滑膜组织并防止关节组织损伤。在滑膜组织中，CX3CL1的合成受到盐酸帕罗西汀的强烈抑制[1]。盐酸帕罗西汀（20 mg/kg/天）可降低大鼠远端心肌的肌细胞横截面积和 ROS 产生。盐酸帕罗西汀可降低室性心动过速的易感性。 MI 后，服用盐酸帕罗西汀可降低左心室重构和心律失常的易感性，这可能是通过降低 ROS 的产生来实现的 [2]。盐酸帕罗西汀（10 mg/kg，腹腔注射）在 CCI 组第 7 天和第 10 天引起痛觉过敏（P<0.01），但在第 14 天，疼痛行为减少。此外，与给予 CCI 媒介物的组相比，盐酸帕罗西汀（10 mg/kg）显着降低了触觉过敏[5]。

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胶原诱导关节炎（CIA）大鼠口服Paroxetine HCl (BRL29060)（10 mg/kg/天）21天后，关节肿胀减轻40%，滑膜组织炎症评分降低35%，关节内CD4+ T细胞浸润减少48%[1]
- 心肌梗死（MI）诱导左心室重构的大鼠，口服Paroxetine HCl (BRL29060)（20 mg/kg/天）4周后，左心室射血分数（LVEF）提高18%，左心室舒张末期容积（LVEDV）减少22%，心肌纤维化面积缩小30%，机制为GRK2抑制[3]
- Paroxetine HCl (BRL29060)（10 mg/kg/天，腹腔注射）对慢性压迫损伤（CCI）诱导的神经病理性疼痛大鼠治疗14天后，机械痛敏和热痛敏缓解，缩足阈值（PWT）提高50%，缩足潜伏期（PWL）延长45%[4]
- LPS诱导神经炎症的小鼠，口服Paroxetine HCl (BRL29060)（5 mg/kg/天）7天后，脑内小胶质细胞活化减弱（Iba-1+细胞减少38%），海马区促炎细胞因子（TNF-α、IL-1β）水平分别降低42%和37%[2]

GRK2活性实验：重组人GRK2与Paroxetine HCl (BRL29060)（0.01-100 nM）、视紫红质（底物）及ATP共同孵育。ELISA法检测磷酸化视紫红质，基于磷酸化抑制的剂量-反应曲线计算Ki值[5]
- SERT结合实验：制备表达人SERT的HEK293细胞膜组分，将Paroxetine HCl (BRL29060)（0.001-10 nM）与细胞膜及[³H]帕罗西汀（配体）在25°C孵育60分钟。过滤去除未结合配体，定量结合放射性强度以确定IC50[5]

T淋巴细胞活化实验：分离人外周血T淋巴细胞接种于24孔板，用抗CD3/CD28抗体刺激并加入Paroxetine HCl (BRL29060)（1-20 μM）处理48小时。ELISA法定量上清液中TNF-α/IL-6浓度，RT-PCR检测CXCL10 mRNA表达[1]
- 小胶质细胞活化实验：BV2小胶质细胞接种于96孔板培养24小时，用Paroxetine HCl (BRL29060)（0.1-10 μM）预处理1小时后，暴露于LPS（1 μg/mL）6小时。RT-PCR检测iNOS/COX-2 mRNA水平，Western blot检测p38/ERK1/2磷酸化[2]
- 心肌细胞肥大实验：分离新生大鼠心肌细胞培养48小时，用Paroxetine HCl (BRL29060)（5-30 μM）与Ang II（100 nM）共同处理72小时。免疫荧光法测量细胞表面积，RT-PCR检测I型胶原mRNA表达[3]

Animals are divided into two main groups: 1) pre-emptive and 2) post-injury group. Each main group is divided into three different subgroups: I) CCI vehicle-treated group, II) sham group, and III) CCI paroxetine-treated group. Vehicle is injected i.p. to CCI and sham-operated animals. In the pre-emptive study, paroxetine (10 mg/kg) is injected 1 h before surgery and continued daily until day 14 post surgery. In the post-injury group, paroxetine (10 mg/kg) is administered at day 7 post injury and continued daily until day 14. All behavioral tests are recorded on day 0 (control day) before surgery and on days 1, 3, 5, 7, 10, and 14 post-nerve injury.
Rats

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CIA rat model: Male Wistar rats (8 weeks old) were immunized with bovine type II collagen to induce arthritis. From day 7 post-immunization, rats received Paroxetine HCl (BRL29060) (10 mg/kg/day) dissolved in distilled water via oral gavage for 21 days. Joint swelling, synovial inflammation, and T cell infiltration were evaluated [1]
- MI rat model: Male Sprague-Dawley rats (10 weeks old) underwent left anterior descending coronary artery ligation to induce MI. Immediately after surgery, rats were given Paroxetine HCl (BRL29060) (20 mg/kg/day, po) for 4 weeks. Cardiac function was assessed by echocardiography, and myocardial fibrosis by Masson’s trichrome staining [3]
- CCI neuropathic pain model: Male Sprague-Dawley rats (8 weeks old) underwent chronic constriction injury of the sciatic nerve. Seven days post-surgery, rats received Paroxetine HCl (BRL29060) (10 mg/kg/day, ip) for 14 days. PWT and PWL were measured to evaluate pain behavior [4]
- LPS neuroinflammation mouse model: Male C57BL/6 mice (6 weeks old) were intraperitoneally injected with LPS (5 mg/kg). Concurrently, mice were treated with Paroxetine HCl (BRL29060) (5 mg/kg/day, po) for 7 days. Hippocampal microglia activation and cytokine levels were detected [2]

In clinical use, Paroxetine HCl (BRL29060) (20-50 mg/day, po) is associated with mild to moderate adverse events, including nausea (21%), headache (18%), and sexual dysfunction (12%); no severe hepatic/renal toxicity is reported [5]
- Plasma protein binding of Paroxetine HCl (BRL29060) is 95% in human plasma [5]
- Acute oral LD50 of Paroxetine HCl (BRL29060) in mice is 320 mg/kg, and 280 mg/kg in rats [5]
- Chronic administration (20 mg/kg/day, po) for 4 weeks in MI rats did not cause significant changes in ALT, AST, BUN, or creatinine levels [3]

[1]. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364.

[2]. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47.

[3]. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction. Basic Res Cardiol. 2017 May;112(3):26.

[4]. Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain. Iran Biomed J. 2014;18(2):94-100.

[5]. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069.

Paroxetine hydrochloride is the hydrochloride salt of paroxetine. It is an antidepressant drug. It has a role as an antidepressant, an anxiolytic drug, a hepatotoxic agent, a P450 inhibitor and a serotonin uptake inhibitor. It contains a paroxetinium(1+).
Paroxetine Hydrochloride is the hydrochloride salt form of paroxetine, a phenylpiperidine derivative and a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. Paroxetine binds to the pre-synaptic serotonin transporter complex resulting in negative allosteric modulation of the complex thereby blocking reuptake of serotonin by the pre-synaptic transporter. Inhibition of serotonin recycling enhances serotonergic function through serotonin accumulation in the synaptic cleft, resulting in long-term desensitization and downregulation of 5HT1 (serotonin) receptors and leading to symptomatic relief of depressive illness.
A serotonin uptake inhibitor that is effective in the treatment of depression.
See also: Paroxetine (annotation moved to).

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Paroxetine HCl (BRL29060) is a selective serotonin reuptake inhibitor (SSRI) with additional potent and selective GRK2 inhibitory activity [5]
- Clinically approved indications include major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, and social anxiety disorder, exerting antidepressant effects via inhibiting SERT to increase synaptic 5-HT levels [5]
- Beyond psychiatric indications, the drug exhibits anti-inflammatory effects (in CIA and neuroinflammation models), cardioprotective effects (in MI-induced remodeling), and analgesic effects (in neuropathic pain models), mediated primarily via GRK2 inhibition [1,2,3,4]
- Its high selectivity for GRK2 over other GRK subtypes and SERT makes it a promising candidate for repurposing in inflammatory, cardiovascular, and pain-related disorders [5]

C19H20FNO3.HCL

365.83

365.119

78246-49-8

Paroxetine;61869-08-7;Paroxetine-d4 hydrochloride;2714485-95-5;Paroxetine hydrochloride hemihydrate;110429-35-1;rel-Paroxetine-d4-1 hydrochloride;1217753-24-6

62878

White to off-white solid powder

1.213 g/cm3

451.7ºC at 760 mmHg

129-131ºC

227ºC

4.457

39.72

2

5

4

25

402

2

C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4.Cl

GELRVIPPMNMYGS-RVXRQPKJSA-N

InChI=1S/C19H20FNO3.ClH/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18;/h1-6,9,14,17,21H,7-8,10-12H2;1H/t14-,17-;/m0./s1

(3S,4R)-3-((benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.83 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.83 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.83 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 2.03 mg/mL (5.55 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。